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STAMFORD, Conn., Feb. 29, 2024 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, announced today that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for nirogacestat, an oral gamma secretase inhibitor, for the treatment of adults with desmoid tumors. If approved, nirogacestat will be the first therapy to receive marketing authorization in the European Union (EU) for the treatment of desmoid tumors. Nirogacestat previously received Orphan Drug designation from the European Commission for the treatment of soft tissue sarcoma. “The validation of our marketing authorization application is an important step towards bringing nirogacestat to patients with desmoid tumors in the European Union who currently do not have an approved therapy,” said Saqib Islam, Chief Executive Officer of SpringWorks. “We look forward to working with the EMA on this important submission.” The MAA submission is based on results from the Phase 3 DeFi trial. In DeFi, nirogacestat met the primary endpoint of improving progression-free survival (PFS), demonstrating a statistically significant improvement over placebo with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p< 0.001). Median PFS was not reached in the nirogacestat arm and was 15.1 months in the placebo arm. Confirmed objective response rate (ORR) based on blinded independent central review of Response Evaluation Criteria in Solid Tumors v1.1 was 41% with nirogacestat versus 8% with placebo (p<0.001); the complete response rate was 7% in the nirogacestat arm and 0% in the placebo arm. Nirogacestat also demonstrated early and sustained improvements in patient-reported outcomes (PROs) measured as of the cycle 10 assessment, including pain (p<0.001), desmoid tumor-specific symptoms (p<0.001), physical/role functioning (p<0.001), and overall health-related quality of life (p≤0.01). Nirogacestat exhibited a manageable safety and tolerability profile. The most common adverse events (>15%) reported in patients receiving nirogacestat were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. The DeFi trial results were published in the March 9, 2023 edition of the New England Journal of Medicine and presented during a Presidential Symposium at the European Society for Medical Oncology Congress 2022.1, 2 “Desmoid tumors can have a significant impact on patients’ lives and there is a pressing need for a new treatment for patients in Europe,” said Bernd Kasper, M.D., Ph.D., University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany and Principal Investigator of the DeFi trial. “In the DeFi trial, nirogacestat demonstrated significant improvements across progression-free survival, objective response rate, and patient-reported outcomes, and had a safety pro supports long-term dosing. These results support that nirogacestat will be a practice-changing therapy if approved by the EMA.” In November 2023, the U.S. Food and Drug Administration approved OGSIVEO™ (nirogacestat) for the treatment of adults with progressing desmoid tumors who require systemic treatment. The U.S. prescribing information includes the following Warnings & Precautions: diarrhea, ovarian toxicity, hepatotoxicity, non-melanoma skin cancers, electrolyte abnormalities, and embryo-fetal toxicity. Please see below for additional Important Safety Information. About Desmoid Tumors Desmoid tumors (sometimes referred to as aggressive fibromatosis, or desmoid fibromatosis) are rare, aggressive, locally invasive tumors of the soft tissues that can be serious, debilitating, and, in rare cases when vital structures are impacted, life-threatening.3,4 Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females. 5,6 In the European Union, the incidence of desmoid tumors is estimated to be approximately 3-5 cases per million per year.7 Although they do not metastasize, desmoid tumors are associated with recurrence rates of up to 77% after surgical resection.5,8,9 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention instead of surgery for most tumor locations requiring treatment.9 About OGSIVEO™ (nirogacestat) OGSIVEO (nirogacestat) is an oral, selective, small molecule gamma secretase inhibitor approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. OGSIVEO is not approved for the treatment of any other indication in the United States, or for any indication in any other jurisdiction by any other health authority. SpringWorks is also evaluating nirogacestat as a potential treatment for patients with ovarian granulosa cell tumors and for patients with multiple myeloma as part of several B-cell maturation agent (BCMA) combination therapy regimens in collaboration with leaders in industry and academia. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Diarrhea: Diarrhea occurred in 84% of patients treated with OGSIVEO. Grade 3 events occurred in 16% of patients. Monitor patients and manage using antidiarrheal medications. Modify dose as recommended. Ovarian Toxicity: Female reproductive function and fertility may be impaired in patients treated with OGSIVEO. Impact on fertility may depend on factors like duration of therapy and state of gonadal function at time of treatment. Long-term effects on fertility have not been established. Advise patients on the potential risks for ovarian toxicity before initiating treatment. Monitor patients for changes in menstrual cycle regularity or the development of symptoms of estrogen deficiency, including hot flashes, night sweats, and vaginal dryness. Hepatotoxicity: ALT or AST elevations occurred in 30% and 33% of patients, respectively. Grade 3 ALT or AST elevations (>5 × ULN) occurred in 6% and 2.9% of patients. Monitor liver function tests regularly and modify dose as recommended. Non-Melanoma Skin Cancers: New cutaneous squamous cell carcinoma and basal cell carcinoma occurred in 2.9% and 1.4% of patients, respectively. Perform dermatologic evaluations prior to initiation of OGSIVEO and routinely during treatment. Electrolyte Abnormalities: Decreased phosphate (65%) and potassium (22%) occurred in OGSIVEO-treated patients. Phosphate <2 mg/dL occurred in 20% of patients. Grade 3 decreased potassium occurred in 1.4% of patients. Monitor phosphate and potassium levels regularly and supplement as necessary. Modify dose as recommended. Embryo-Fetal Toxicity: Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at maternal exposures below human exposure at the recommended dose of 150 mg twice daily. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose. ADVERSE REACTIONS The most common (≥15%) adverse reactions were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. Serious adverse reactions occurring in ≥2% of patients were ovarian toxicity (4%). The most common laboratory abnormalities (≥15%) were decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium. DRUG INTERACTIONS CYP3A Inhibitors and Inducers: Avoid concomitant use with strong or moderate CYP3A inhibitors (including grapefruit products, Seville oranges, and starfruit) and strong or moderate CYP3A inducers. Gastric Acid Reducing Agents: Avoid concomitant use with proton pump inhibitors and H2 blockers. If concomitant use cannot be avoided, OGSIVEO can be staggered with antacids (e.g., administer OGSIVEO 2 hours before or 2 hours after antacid use). Consult the full Prescribing Information prior to and during treatment for important drug interactions. To report suspected adverse reactions, contact SpringWorks Therapeutics at 1-888-400-SWTX (1-888-400-7989) or FDA at 1-800-FDA-1088 or Please see full U.S. Prescribing Information for OGSIVEO for more information. About SpringWorks Therapeutics SpringWorks is a commercial-stage biopharmaceutical company applying a precision medicine approach to developing and delivering life-changing medicines for people with severe rare diseases and cancer. OGSIVEO™ (nirogacestat), approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment, is the Company’s first FDA-approved therapy. SpringWorks also has a diversified targeted therapy pipeline spanning solid tumors and hematological cancers, with programs ranging from preclinical development through advanced clinical trials. In addition to its wholly owned programs, SpringWorks has also entered into multiple collaborations with innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients in need. For more information, visit and follow @SpringWorksTx on X (formerly Twitter), LinkedIn, and YouTube. SpringWorks Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, relating to our business, operations, and financial conditions, including but not limited to current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our development and commercialization plans, our preclinical and clinical results, the market potential of OGSIVEO for adult patients with desmoid tumors, expectations regarding timing and results of the EMA’s review of the MAA for nirogacestat, including the adequacy of the data contained in the MAA to serve as the basis for marketing approval of nirogacestat for the treatment of desmoid tumors in the European Union, as well as relating to other future conditions. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “would,” “should” and “could,” and similar expressions or words, identify forward-looking statements. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Any forward-looking statements in this presentation are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this presentation, including, without limitation, risks relating to: (i) our expectations regarding the potential clinical benefit of nirogacestat for patients with desmoid tumors, (ii) estimates regarding the number of adult patients who are diagnosed with desmoid tumors annually per year in Europe and the potential market for nirogacestat, (iii) the fact that topline or interim data from clinical studies may not be predictive of the final or more detailed results of such study or the results of other ongoing or future studies, (iv) the timing of our planned regulatory submissions and interactions, including the timing and outcome of decisions made by the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, (v) whether FDA, EMA, or other regulatory authorities will require additional information or further studies, or may fail or refuse to approve or may delay approval of our product candidates, including nirogacestat and mirdametinib, (vi) our ability to obtain regulatory approval of any of our product candidates or maintain regulatory approvals granted for our products, (vii) our ability to maintain adequate patent protection and successfully enforce patent claims against third parties, and (viii) our ability to meet any specific milestones set forth herein. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. For further information regarding the risks, uncertainties and other factors that may cause differences between SpringWorks’ expectations and actual results, you should review the “Risk Factors” in Item 1A of Part I of SpringWorks’ Annual Report on Form 10-K for the year ended December 31, 2023, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings. Contacts Kim Diamond Vice President, Communications and Investor Relations Phone: 203-561-1646 Email: kdiamond@springworkstx.com Samantha Hilson Sandler Senior Director, Investor Relations Phone: 203-461-5501 Email: samantha.sandler@springworkstx.com References 1 Gounder M, Ratan R, Alcindor T, et al. Nirogacestat, a Gamma-Secretase Inhibitor for Desmoid Tumors. N Engl J Med. 2023;388:898-912. doi:10.1056/NEJMoa2210140. 2 Kasper B, Ratan R, Alcindor T, et al. DeFi: A phase III, randomized controlled trial of nirogacestat versus placebo for progressing desmoid tumors (DT). Ann Oncol. 2022;33(suppl_7): S808-S869. 3 Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives. Pathologica. 2021;113(2):70-84. doi:10.32074/1591-951X-213. 4 Penel N, Chibon F, Salas S. Adult desmoid tumors: biology, management and ongoing trials. Curr Opin Oncol. 2017;29(4):268-274. doi:10.1097/CCO.0000000000000374. 5 Skubitz KM. Biology and treatment of aggressive fibromatosis or desmoid tumor. Mayo Clin Proc. 2017;92(6):947-964. doi:10.1016/j.mayocp.2017.02.012. 6 van Broekhoven DLM, Grünhagen DJ, den Bakker MA, van Dalen T, Verhoef C. Time trends in the incidence and treatment of extra-abdominal and abdominal aggressive fibromatosis: a population-based study. Ann Surg Oncol. 2015;22(9):2817-2823. doi:10.1245/s10434-015-4632-y. 7 Orphanet Report Series: Rare Diseases collection. Prevalence and incidence of rare diseases: bibliographic data. January 2019. . 8 Easter DW, Halasz NA. Recent trends in the management of desmoid tumors. Summary of 19 cases and review of the literature. Ann Surg. 1989;210(6):765-769. doi:10.1097/00000658-198912000-00012. 9 Gronchi A, Kasper B, et al. Desmoid Tumor Working Group. The management of desmoid tumours: a joint global consensus-based guideline approach for adult and paediatric patients. Eur J Cancer. 2020;127:96-107. doi:10.1016/j.ejca.2019.11.013.

“Hot flushes and night sweats caused by menopause are common, and can have a significant impact on a woman’s daily life. We are therefore pleased to have authorised Veoza (fezolinetant) for hot flushes and night sweats caused by menopause via our reliance procedure,” said Julian Beach, interim executive director of healthcare quality and access at the MHRA, to the Guardian on Sunday ​. “No medicine would be approved unless it met our expected standards of safety, quality and effectiveness, and we continue to keep the safety of all medicines under close review.” Hot flashes, also known as vasomotor symptoms, can occur during the menopause in women aged between 40 and 64 as estrogen levels decline and the body is less able to regulate its temperature. While hormonal treatments can be effective in many people, not all patients can benefit and the therapies can increase the risk ​ of cardiovascular diseases and cancer. As an oral non-hormonal treatment, Veoza has the potential to treat hot flashes in women that cannot benefit from hormonal therapy. The drug blocks the action of a signalling molecule called neurokinin B on a specific type of neuron in the brain’s temperature control centre called the hypothalamus. According to phase 3 results in March 2023, the drug significantly reduced the frequency and severity of vasomotor symptoms compared to a placebo, kicking in as early as week 1 in the trial. However, the treatment is not designed to treat other menopausal symptoms such as mood changes or vaginal dryness. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Astellas says the drug will initially be available only with a prescription and privately from January 5th, 2024. The company is also applying for approval for use of the drug in the National Health Service (NHS).

Priyanka Jain, CEO and co-founder of vaginal health company Evvy, felt more like an educator rather than an entrepreneur when she first set out to raise funds for her startup. The company, which has raised $19 million since inception in 2021, is direct-to-consumer and sells at-home vaginal microbiome tests. Questions she received from investors — mostly men — included: What’s a yeast infection? Is it really that frustrating? Is this really a problem? Indeed, up to 75% of women or people assigned female at birth will have at least one vaginal yeast infection in their life. But with the male-dominated venture capital industry (just 8.6% of venture capitalists are women), many investors simply aren’t aware of these facts. “You have to start with the barrier of what even is this condition, educating them about it, then talking about the prevalence, then talking about the standard of care,” Jain said in an interview. “So it just takes a lot longer for them to jump through the things they have to believe in order to believe in the company.” Jain’s barriers in raising funds are not unique and are faced by many founders of startups that focus on stigmatized women’s health conditions. Despite women representing half of the population, just 3% of digital health funding focused on women’s health between 2011 and 2020, and a majority goes to startups addressing fertility, pregnancy and motherhood, according to Rock Health. But do startups that focus on male stigmatized conditions face the same challenges in raising funds? There is no clear answer. ‘I’ll ask my wife about this’ One experience, in particular, is common to the interaction between women entrepreneurs and men investors: being told they’ll ask their assistant or wife about the condition the company treats. “Obviously, I don’t think anyone wants to talk to their boss about vaginal odor,” Jain remarked with incredulity. “There are plenty of people saying, ‘I’ll ask my wife about this.’ It was kind of frustrating to feel like we were being passed off to people who weren’t investors to evaluate the opportunity, because there were no investors available who had vaginas to help evaluate it.” Jain added that she often feels bad for these women associates who may have to have these uncomfortable, private conversations with their bosses to bring them up to speed on how big of a problem it is for women — and in order for women’s health startups to get funding. Stephanie Estey, co-founder of sexual health company TBD Health in New York City, has had similar challenges with a male VC bringing along his female associate or saying he needs to show the startup’s products to his wife. Despite serving all genders, the company often gets put into a “women’s health box.” The direct-to-consumer company’s services include STI testing and contraceptives. It has raised a little under $5 million. Another women’s health founder, Ellen Rudolph, said she often experienced issues where men investors “wrote me off in the beginning and weren’t paying attention.” Her company, Atherton, California-based WellTheory, serves consumers and employers and offers care for autoimmune conditions, which primarily affect women. The startup has raised $7.2 million. “I had one male investor who said, ‘I believe that there’s a billion-dollar company to be built in this space, but I don’t know if you or I know what that is.’ And I will never forget that,” Rudolph said. “I think the challenge is a little bit that there’s this dissonance because a lot of the time the person you’re pitching to doesn’t have that lived experience or understanding.” All of the above is reason enough for VC firms to hire women partners or promote them to those positions. But it’s not always male investors distancing themselves from women’s health companies. Sometimes it’s women investors who are trying to “diversify away” from the women’s health space, according to Estey. “I think some of the more surprising things have actually been when female investors — who may naturally have empathy for what we’re doing at TBD — actively don’t want to invest in a category that’s often associated with women’s health,” she said. “So they actively try to not invest in women’s health or try to invest in something that is more like FinTech or crypto or something very different.” Rachel Blank, CEO and founder of New York City-based Allara Health, agreed that it’s not always men who question women’s health startups when they’re seeking funding. Allara, which has raised about $16.5 million, is a digital health company that treats gynecological conditions like polycystic ovary syndrome (PCOS) and endometriosis. Blank said she received comments from both men and women who thought there wasn’t a big enough market for her company. But once she explained the data that PCOS affects about one in 10 women of reproductive age — as does endometriosis — investors were receptive. That’s not to say all conversations with investors were met with the kind of passive cluelessness that the women’s health founders shared. Jain said that when talking to women investors, her experience was “split between people who were like ‘Oh my god, this is me’ … and women who were like ‘Huh, I’m now realizing how lucky I’ve been to not be in the cycle of recurrent [vaginal] infections.’” Evvy has also received funding from Virtue, which is led by male investors Sean Doolan and Emre Karatas, who Jain said were receptive to Evvy’s endeavors. “From my first conversation with them, they were like, ‘Wow, there’s so much we don’t know here. We’re gonna go get educated,’” Jain said. “And they came back actually with an unbelievable set of information for me of, ‘Here’s how massive this opportunity is. And we did all this research, and here’s what we learned.’ I was just so amazed by their willingness to learn and desire to really be educated on it.” Do men’s health companies have the same challenges? When direct-to-consumer telemedicine company Hims & Hers started out around 2017, it primarily focused on conditions like erectile dysfunction and hair loss in men. The San Francisco-based company has since expanded into other men’s health conditions, as well as women’s health, and is now public. Before going public, it had raised about $200 million. Melissa Baird, COO of Hims & Hers, said that when seeking funding in the early days, there was some investor discomfort. And since erectile dysfunction isn’t a commonly talked about subject, she said that there were often men and women investors who said that they didn’t know anybody who had this condition, even though statistically speaking they probably did and just didn’t know it. About 30 million men in the U.S. are affected by erectile dysfunction. “I’ve been in meetings where fully grown men would giggle when I mentioned erectile dysfunction, so there definitely was a [taboo] element to it,” Baird said. But once the company started explaining how big of a market there is for its services, “it stopped the giggling pretty fast,” she added. Meanwhile, Maple Grove, Minnesota-based Morari, an early-stage startup focused on premature ejaculation, has had its own struggles in raising funds. The medical device company offers a wearable skin patch that helps delay ejaculation during sex. So far, the company has raised about $3 million from friends, family and angel investors. But when it comes to venture capital funding, the company’s challenges often come from the fact that its product doesn’t have FDA approval yet, according to CEO and Founder Jeff Bennett. He added that there is also an element of discomfort around the topic, “but they don’t come out and say that, they just say it’s not a fit for us.” In this case, he often doesn’t get further information on why the VC chose to pass on the company. “I think anything about sexual health and wellness, given the taboo nature of it, it’s going to be difficult,” Bennett said. What the investors say Several investors agree that women’s health companies focused on stigmatized conditions likely struggle more to get funding than their men’s health counterparts, but said they don’t have the data to prove it. These struggles are most likely due to “who’s in the room,” hinting at the fact that there are more male investors than female, according to Alyssa Jaffee, partner at 7wireVentures. Jaffee has looked at companies for vaginal dryness, PCOS and postpartum leakage. She said she didn’t make an investment in these companies, but not because there wasn’t an opportunity in the space. Rather, it was that the company wasn’t the right fit, she said. “This is health, this is healthcare, this shouldn’t be icky,” Jaffee said. “I think that if you had people in a room who didn’t feel as comfortable with the topic, I can imagine that it would feel that way.” However, 7wireVentures has invested in women’s health companies like Parsley Health, which treats autoimmune conditions, digestive issues, fertility and other areas. It’s also invested in Caraway, which specializes in treating Gen Z women and offers mental, physical and reproductive virtual health. Sean Doolan, founder and managing partner of Virtue, also noted that some of the struggles women’s health companies face may be because there are fewer women VCs. In addition to investing in Evvy, Doolan also invested in Allara before creating Virtue. “I don’t think it’s necessarily controversial to say that a majority of investors are still men. And from both personal and professional experience, I think more men than not might be uncomfortable with having certain conversations about women’s health that they can’t directly relate to.” However, despite this, Doolan noted that he sees far fewer pitches for men’s health than he does for women’s health. Kerry Rupp, general partner of True Wealth Ventures, agreed that women’s health companies face additional challenges, and it partially goes back to the fact that women weren’t included in medical research until relatively recently. In addition, some of these companies struggle with advertising due to the censorship of sexual health information for women. True Wealth Ventures invests in women-led businesses. “I think investors think, ‘Oh, that’s a mess, we don’t want to get into it.’ So not only do they not necessarily understand or want to talk about the women’s health issue, but then they’re also like, ‘Oh, it’s harder for you to actually execute on your customer acquisition strategy,’” Rupp said. Despite these challenges, Rupp has invested in a women’s sexual health company called Rosy, which offers wellness plans for issues like body image, sexual pain, sexual trauma and other areas. She chose to invest in Rosy because it was able to show proof of positive outcomes and that its services are evidence-based. Another investor, while noting that women’s health companies have an uphill battle with the lack of women in the VC world, added that there is another challenge that these startups face that doesn’t have to do with gender. While these types of companies may be successful in a direct-to-consumer business model, it may be harder for them to succeed in a B2B model, according to Ellen Herlacher, partner at LRVHealth. “When you look at a payer, who is probably unlikely to take their eye off the ball from oncology, cardiology, MSK — the things that are very clear cost drivers — and say there are incremental cost savings that you could provide by covering this pelvic floor offering, it’s just never going to rise to the priority because it doesn’t represent a high enough medical cost,” Herlacher said. “On the employer side, there’s just a good amount of fatigue,” she continued. “Employers have done a great job of moving the boulder up the hill when it comes to things like fertility, when it comes to things like access to a variety of services that accompany maternity. But I think it’s going to be hard to convince an employer that they’re going to impact culture or medical costs if they cover at-home STI testing.” Lead with the data What do investors want from the startups pitching to them? Proof and data that their company can make a difference, several investors said. For Doolan, this is what Evvy and Allara provided. “We want to go beyond just the narrative that might catch some emotional strings,” he said. “How does that translate to more of a measurable understanding?” Rupp echoed Doolan’s comments. Showing information like how many people the company could impact and what the financial opportunity is “could be the thing that excites investors,” she said. And when it comes to addressing uncomfortable, stigmatized topics, Herlacher said it’s important to not shy away. “Take it head on,” she said. “Own the fact that it’s uncomfortable. Take on the responsibility of educating the people around the room and then take on the responsibility of explaining why there’s a big business here.”